The Dysbiosis and Inter-Kingdom Synergy Model in Oropharyngeal Candidiasis, a New Perspective in Pathogenesis

Abstract

As more information emerges on oral microbiota using advanced sequencing methodologies, it is imperative to examine how organisms modulate the capacity of each other to colonize or trigger infection. Most mouse models of oral C. albicans infection have focused on interactions with single bacterial species. Thus, little is known about the microbiome-mediated interactions that control the switch of C. albicans from commensalism to infection. Evidence is accumulating that in immunosuppression where mucosal candidiasis is more prevalent, there is an altered oral bacterial microbiome with reduced diversity, but not an altered mycobiome. Oropharyngeal candidiasis in immunosuppressed humans and mice is associated with a further reduction in oral bacterial diversity and a dysbiotic shift with significant enrichment of streptococcal and enterococcal species. Our recent studies in a cancer chemotherapy mouse model supported the combined profound effect of immunosuppression and C. albicans in reducing oral bacterial diversity and provided the first direct evidence that these changes contribute to pathogenesis, representing dysbiosis. There is still a gap in understanding the relationship between Candida and the oral bacterial microbiome. We propose that certain oral commensal bacteria contribute to fungal pathogenesis and we identify gaps in our understanding of the mechanisms involved in this cooperative virulence.

Anticandidal Activities by Lactobacillus Species: An Update on Mechanisms of Action

“…The presence, composition, and metabolic stage of the resident microbiota may affect the efficacy of Lactobacillus species used as probiotics. For example, while lactobacilli modulate the growth and morphologic transition of Candida in vitro, murine studies show that Candida overgrowth may reduce the abundance of oral lactobacilli, favoring an enterococcus-rich dysbiosis, as recently demonstrated by our group [17,23]. Moreover, Candida may prevent the restoration of the healthy microbiota post-antibiotics, by inhibiting Lactobacillus spp in th murine gut [40].…”

“…Moreover, under a dysbiotic scenario, some pathobionts (commensals that can turn into opportunistic pathogens) may form synergistic interactions with each other, leading to severe infections. Recently, Bertolini et al showed that oral bacterial pathobionts facilitate fungal infection by increasing the expression of virulence genes in C. albicans or disrupting the mucosal barrier via proteolytic enzymes [ 23 ]. Hong et al suggested oral microbiota disruption is associated with oral mucositis, exacerbating epithelial injury in cancer patients receiving cytotoxic chemotherapy [ 15 ].…”

Priority effects dictate community structure and alter virulence of fungal-bacterial biofilms

“…The most common fungal and bacterial species detected in DFU are Candida albicans and Staphylococcus aureus , found in 47 and 95% of DFUs respectively [ 6 – 8 , 13 , 15 , 16 , 26 , 33 ]. Interactions between these species are synergistic and enabled via cell-cell adhesion and cross-feeding mechanisms [ 34 – 36 ]. Attachment of S. aureus to C. albicans in biofilms is well studied [ 37 , 38 ] and serve as model for studying cross-kingdom interactions [ 39 – 42 ].…”

Counter-Acting Candida albicans-Staphylococcus aureus Mixed Biofilm on Titanium Implants Using Microbial Biosurfactants

“…Candida albicans is the most frequently isolated fungal species in the oral cavity [ 22 ]. Although it is a human commensal species, under certain conditions, such as the use of antibiotics, immunosuppressive treatments or immune-depressive diseases, and reduced salivation, it can cause infections of the oral mucosa [ 23 , 24 , 25 ]. In addition, due to its high capacity to form biofilms, it can colonize abiotic surfaces, such as prostheses and dental implants, being involved in the etiology of peri-implantitis [ 8 , 26 , 27 ].…”